Highlights in aggressive lymphoma

In this video, Dr William Basem, haematologist at the OhioHealth Physician Group in Columbus, Ohio, shares some of the key take aways of an oral abstract session at ASH 2024 focussing on innovative, chemotherapy-free treatment options for patients with aggressive B-cell lymphomas.

In recent years, the increased efficacy of next generation Bruton tyrosine kinase inhibitors (BTKi) and bispecific antibodies has opened the door towards chemotherapy-free treatment regimens for patients with an aggressive B-cell lymphoma. During ASH 2024, promising results of several of these novel combinations have been presented, demonstrating unprecedented response rates in often heavily pretreated patients.

In a first of these studies, the combination of glofitamab and polatuzumab vedotin was shown to be associated with an objective response rate (ORR) of about 80% in a cohort of 129 patients with R/R large B-cell lymphoma (LBCL). In 62% of patients a complete response was noted. Patients in this trial received a median of 2 prior treatment lines (range: 1-7), with 71% being refractory to the last line of therapy and 22% being pretreated with CAR-T cell therapy. Interestingly, the study also included 44 patients with a high-grade B-cell lymphoma (HGBCL) in whom an ORR and CR rate of respectively 79.5% and 65.9% were reported. Among the CAR-T pretreated patients the ORR reached 75%, with a CR in 50%.1  

A second abstract was selected by Dr Basem discussed the results obtained with a combination of glofitamab with rituximab and ICE (Ifosfamide, carboplatin, and etoposide) in patients with R/R Diffuse Large B-Cell Lymphoma (DLBCL) who were eligible for a stem cell transplantation or CAR-T therapy.2 In this phase Ib study, the glofitamab-rituximab-ICE combination was given in 2nd line and resulted in an ORR of 76.9% (CR: 23.1%) in patients with primary refractory disease and 86.2% in patients with a disease relapse (CR: 13.8%). Interestingly, all 8 patients with a rapid relapse obtained an ORR in this study, with 2 of them having a CR.2 As such, these findings are much better than historical data from the SCHOLAR trial in which the ORR only reached about 40%.

In another phase I study, the combination of the BTKi acalabrutinib and the immune checkpoint inhibitor durvalumab was evaluated in a cohort of 13 patients with primary central nervous system lymphoma (PCNSL). To be eligible for this study, patients had to be pretreated with >1 CNS-directed therapy. The acalabrutinib-durvalumab combination induced an ORR 40% (all CRs), with a median response duration of about 9 months. Interestingly, acalabrutinib was detected in the cerebrospinal fluid of 5 out of 8 evaluated patients providing evidence for the CNS penetrating potential of this agent.3

Finally, Dr Basem touched upon the results of a phase I study evaluating the combination of glofitamab and englumafusp alfa in patients with R/R B-cell non-Hodgkin lymphoma. Englumafusp alfa is a co-stimulatory antibody-like fusion protein targeting CD19 on B cells and 4-1BB on immune cells. In the subgroup of patients with an aggressive lymphoma (N= 83) a best overall response rate (BOR) of 68.6% was reported, with a CR in 56.6% and a median response duration of 25.9 months. Response rates were higher among patients who received the regimen in second line (BOR 76.9%, all CRs) and in patients who did not previously receive CAR-T therapy (BOR 73.2%, CR: 65.9%).4